MONARCH: Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic Chronic Hepatitis B Virus (HBV)

• Sponsor: Arrowhead Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02577029
• Collaborator: (none)
• Enrollment: 79
• Locations: 33
• Arms: 8
• Actual Duration (Months): 12
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Patients with chronic HBV infection will receive either ARC-520 alone or ARC-520 in combination with other treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated interferon (PEG IFN) alpha 2a therapy, and be evaluated for safety and efficacy.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; Hepatitis D	Drug: ARC-520; Drug: entecavir; Biological: pegylated interferon alpha 2a; Drug: tenofovir disoproxil; Drug: antihistamine	Phase 2

Detailed Description

This is a multicenter, open-label study of ARC-520 based treatment regimens administered to patients with HBeAg positive or HBeAg negative immune active chronic Hepatitis B Virus (HBV) infection of various genotypes, or patients with Hepatitis D Virus (HDV). Eligible patients naive to previous treatment, and who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 alone or ARC-520 plus additional treatments such as entecavir (ETV) or tenofovir (TDF) and/or pegylated interferon alpha 2a (PEG IFN) therapy. The study may initially involve up to a total of 96 eligible chronic HBV and HDV infected patients. Patients in all cohorts will receive a total of 13 doses of ARC-520 at 2mg/kg or 4 mg/kg. Patients will undergo the following evaluations at regular intervals during the study: medical history, physical examinations, vital sign measurements (blood pressure, heart rate, respiratory rate, and temperature), weight, adverse events assessment (AEs), 12-lead ECGs, liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation, chemistry, exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, cytokines, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) and pregnancy testing for females of childbearing potential. Clinically significant changes including AEs will be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or until the patient is lost to follow-up. For each patient, the duration of the study is approximately 96 weeks, from enrolment to last visit. Prior to enrolment there is a 60 day screening period. Addition of new cohorts and additional treatment regimens are anticipated for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label Study to Evaluate ARC-520 Administered Alone and in Combination With Other Therapeutics in Patients With Chronic Hepatitis B Virus (HBV) Infection (MONARCH)
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Treatment-naïve, hepatitis B "e" antigen (HBeAg)-positive participants with chronic hepatitis B (CHB) of any genotype administered ARC-520 (2 mg/kg intravenous [IV]) every 4 weeks for 48 weeks (13 doses).	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 2 Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered peginterferon (PEG IFN) alpha 2a for 48 weeks starting Day 87.	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: entecavir; 0.5 mg once daily; oral; Other Names: Baraclude ; Biological: pegylated interferon alpha 2a; 180 mcg; subcutaneous injection once weekly; Other Names: Peginterferon Pegasys ; Drug: tenofovir disoproxil; 300 mg once daily; oral; Other Names: Viread ; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 3 Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: entecavir; 0.5 mg once daily; oral; Other Names: Baraclude ; Biological: pegylated interferon alpha 2a; 180 mcg; subcutaneous injection once weekly; Other Names: Peginterferon Pegasys ; Drug: tenofovir disoproxil; 300 mg once daily; oral; Other Names: Viread ; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 4 Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: entecavir; 0.5 mg once daily; oral; Other Names: Baraclude ; Biological: pegylated interferon alpha 2a; 180 mcg; subcutaneous injection once weekly; Other Names: Peginterferon Pegasys ; Drug: tenofovir disoproxil; 300 mg once daily; oral; Other Names: Viread ; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 5 Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: entecavir; 0.5 mg once daily; oral; Other Names: Baraclude ; Biological: pegylated interferon alpha 2a; 180 mcg; subcutaneous injection once weekly; Other Names: Peginterferon Pegasys ; Drug: tenofovir disoproxil; 300 mg once daily; oral; Other Names: Viread ; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 6 Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: entecavir; 0.5 mg once daily; oral; Other Names: Baraclude ; Biological: pegylated interferon alpha 2a; 180 mcg; subcutaneous injection once weekly; Other Names: Peginterferon Pegasys ; Drug: tenofovir disoproxil; 300 mg once daily; oral; Other Names: Viread ; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 7 Treatment-naïve, HBeAg-negative or HBeAg-positive participants with hepatitis delta virus (HDV) administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Biological: pegylated interferon alpha 2a; 180 mcg; subcutaneous injection once weekly; Other Names: Peginterferon Pegasys ; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Experimental: Cohort 8 Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Drug: ARC-520; ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.; Drug: antihistamine; All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving a 1-log Reduction in Hepatitis B Surface Antigen (HBsAg) at Week 60 Compared to Baseline [Baseline, Week 60]

   The percentage of participants with chronic HBV achieving a 1-log reduction in HBsAg compared to baseline (mean of pre-dose values) at Week 60 after completion of 48 weeks of ARC-520 Injection.

Secondary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Considered Possibly or Probably Related to Treatment [From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up]

   The Principal Investigator (or medically qualified designee) will use clinical judgment to determine the relationship. An adverse event (AE) was considered "possibly related" when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the product under investigation. An AE was considered "probably related" when there are facts, evidence, or arguments to suggest that the event is related to the product under investigation. Only AEs that occurred post-dose were considered treatment-emergent. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs.

2. Percentage of Participants With HBsAg Loss (Based on Qualitative Assay) Over Time [Weeks 52, 60, 72 and 96]

   The qualitative HBsAg assay gives a binary result, positive or negative.

3. Percentage of Participants Achieving a 1-log Reduction in HBsAg and Achieving an HBsAg Level < 100 IU/L Over Time [Weeks 52, 60, 72 and 96]

4. Time to HBsAg Loss [Baseline through Week 96]

5. Time to Anti-HBs (Antibody to Hepatitis B Surface Antigen) Seroconversion [Baseline through Week 96]

6. Percentage of Participants With Anti-HBs Seroconversion Over Time [Weeks 52, 60, 72 and 96]

7. Percentage of Participants With HBeAg Loss and Anti-Hepatitis B e Antigen (Anti-HBe) Seroconversion (if HBeAg-Positive at Study Entry) Over Time [Weeks 52, 60, 72 and 96]

8. Percentage of Participants With Resistance to ARC-520 Injection by Week 52 [Week 52]

   Resistance is defined as > 1.0 log IU/mL quantitative HBsAg (qHBsAg) increase from nadir, confirmed by repeat test.

9. Percentage of Participants With Resistance to the Combination Therapy From Baseline to Week 60 [Baseline, Week 60]

   Resistance is defined as > 1.0 log IU/mL increase in HBV DNA from nadir, confirmed by repeat test.

10. Percentage of Participants With HDV With Undetectable HDV Ribonucleic Acid (RNA) After 48 Weeks of Concomitant ARC-520 Injection and PEG IFN Alpha 2a Therapy Over Time (Cohort 7 Only) [Weeks 52, 60, 72 and 96]

11. Log Change From Baseline in Quantitative HBV Deoxyribonucleic Acid (DNA) Serum Levels Over Time [Baseline, Weeks 52, 60, 72 and 96]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, 18 to 75 years of age

• Written informed consent

• No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment

• Diagnosis of HBeAg negative or positive chronic HBV infection.

• Must be HBsAg (+) during screening.

• Must be treatment naïve: never on PEG IFN alpha 2a and/or ETV or TDF; and

• Have not used nucleoside/nucleotide analogs (NUCs) within the last 2 years prior to dosing on Day 1

• Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners)

Exclusion Criteria:

• Pregnant or lactating

• Acute signs of hepatitis/other severe infections within 4 weeks of screening

• Use within the last 14 days or anticipated requirement for anticoagulants, systemic corticosteroids, immunomodulators, or immunosuppressants

• Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, over-the-counter (OTC) and prescription pain medication or hormonal contraceptives

• History of poorly controlled autoimmune disease or any history of autoimmune hepatitis

• History of heterozygous or homozygous familial hypercholesterolemia.

• Human immunodeficiency virus (HIV) infection

• Is sero-positive for Hepatitis C Virus (HCV), or has a history of delta virus hepatitis (except for cohort in which delta virus infection is acceptable)

• Has hypertension: blood pressure > 170/100 mmHg; well-controlled blood pressure on hypertensive medication allowed

• History of cardiac rhythm disturbances

• Family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death

• Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry

• History of malignancy, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer

• Has had major surgery within 1 month of screening

• Regular use of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week)

• Use of recreational drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to the screening

• History of allergy to bee sting

• Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's disease, hemochromatosis, or alpha-1 antitrypsin deficiency

• Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction

• Clinically significant history or presence of poorly controlled/uncontrolled systemic disease

• Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk

• History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
2	Concord Repatriation General Hospital, Gastroenterology & Liver Services	Concord	New South Wales	Australia	2139
3	St. Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
4	Westmead Hospital	Westmead	New South Wales	Australia	2145
5	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
6	Monash Health Clayton Campus	Clayton	Victoria	Australia	3168
7	St. Vincent's Hospital Melbourne	Fitzroy	Victoria	Australia	3065
8	Royal Melbourne Hospital	Parkville	Victoria	Australia	3052
9	Linear Clinical Research Ltd.	Nedlands	Western Australia	Australia	6009
10	MHAT St. Pantaleimon OOD, Department of Gastroenterology	Pleven		Bulgaria	5800
11	UMHAT St. Ivan Rilski EAD, Clinic of Gastroenterology	Sofia		Bulgaria	1431
12	Diagnostic and Consultative Center - Focus 5 - Outpatient Medical Center, EOOD	Sofia		Bulgaria	1463
13	Diagnostic and Consultative Center Mladost-M Varna	Varna		Bulgaria	9020
14	Queen Mary Hospital, Department of Medicine	Hong Kong		China
15	Pusan National University Hospital	Busan		Korea, Republic of	49241
16	Inje University Busan Paik Hospital	Busan		Korea, Republic of
17	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
18	Seoul National University Hospital	Seoul		Korea, Republic of	3080
19	Gangnam Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	6273
20	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of
21	IMSP Spitalul Clinic de Boli Infectioase, Toma Ciorba	Chisinau		Moldova, Republic of	MD-2004
22	Middlemore Clinical Trials, Middlemore Hospital	Papatoetoe	Aukland	New Zealand	2025
23	Dunedin Hospital, Gastroenterology Research Unit	Dunedin	Otago-Southland	New Zealand
24	Auckland Clinical Studies	Auckland		New Zealand	1010
25	National Taiwan University Hospital, Yun-Lin Branch	Douliou	Yunlin County	Taiwan	640
26	Changhua Christian Hospital	Changhua		Taiwan	500
27	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
28	King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
29	Hospital of Tropical Diseases	Bangkok		Thailand	10400
30	Phramongkutklao Hospital, Division of Digestive and Liver Disease	Bangkok		Thailand	10400
31	Maharaj Nakhon Chiang Mai Hospital, Gastroenterology Division	Chiang Mai		Thailand	50200
32	Khon Kaen University	Khon Kaen		Thailand	40002
33	Thammasat University Hospital, Gastroenterology Unit	Pathumthani		Thailand	12120

Sponsors and Collaborators

• Arrowhead Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Arrowhead Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02577029
• Other Study ID Numbers: Heparc-2008; 2015-005499-46
• First Posted: Oct 15, 2015
• Last Update Posted: Apr 12, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis D; Hepatitis; Interferons; Tenofovir; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; Entecavir; Histamine Antagonists; Histamine H1 Antagonists

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, hepatitis B "e" antigen (HBeAg)-positive participants with chronic hepatitis B (CHB) of any genotype administered ARC-520 (2 mg/kg intravenous [IV]) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered entecavir (ETV) or tenofovir (TDF) for approximately 60 weeks starting Day 1 and weekly subcutaneously administered peginterferon (PEG IFN) alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with hepatitis delta virus (HDV) administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Period Title: Overall Study
STARTED	10	2	7	12	11	13	12	12
COMPLETED	0	0	0	0	0	0	0	0
NOT COMPLETED	10	2	7	12	11	13	12	12

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Total
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Total of all reporting groups
Overall Participants	10	2	7	12	11	13	12	12	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.5 (11.09)	29.5 (0.71)	40.4 (7.37)	36.3 (9.32)	39.6 (12.61)	38.2 (7.97)	39.6 (7.73)	36.7 (7.32)	37.4 (9.17)
Sex: Female, Male (Count of Participants)
Female	7 70%	1 50%	4 57.1%	6 50%	3 27.3%	2 15.4%	6 50%	5 41.7%	34 43%
Male	3 30%	1 50%	3 42.9%	6 50%	8 72.7%	11 84.6%	6 50%	7 58.3%	45 57%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving a 1-log Reduction in Hepatitis B Surface Antigen (HBsAg) at Week 60 Compared to Baseline
Description	The percentage of participants with chronic HBV achieving a 1-log reduction in HBsAg compared to baseline (mean of pre-dose values) at Week 60 after completion of 48 weeks of ARC-520 Injection.
Time Frame	Baseline, Week 60

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 60 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

2. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Considered Possibly or Probably Related to Treatment
Description	The Principal Investigator (or medically qualified designee) will use clinical judgment to determine the relationship. An adverse event (AE) was considered "possibly related" when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the product under investigation. An AE was considered "probably related" when there are facts, evidence, or arguments to suggest that the event is related to the product under investigation. Only AEs that occurred post-dose were considered treatment-emergent. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs.
Time Frame	From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	10	2	7	12	11	13	12	12
Related TEAE	1 10%	0 0%	3 42.9%	2 16.7%	3 27.3%	4 30.8%	3 25%	3 25%
Related Serious TEAE	0 0%	0 0%	0 0%	0 0%	0 0%	1 7.7%	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With HBsAg Loss (Based on Qualitative Assay) Over Time
Description	The qualitative HBsAg assay gives a binary result, positive or negative.
Time Frame	Weeks 52, 60, 72 and 96

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

4. Secondary Outcome

Title	Percentage of Participants Achieving a 1-log Reduction in HBsAg and Achieving an HBsAg Level < 100 IU/L Over Time
Time Frame	Weeks 52, 60, 72 and 96

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

5. Secondary Outcome

Title	Time to HBsAg Loss
Time Frame	Baseline through Week 96

Outcome Measure Data

Analysis Population Description

This analysis was not done since no events of HBsAg loss were observed to to Week 36. (No participant reached Week 96 of treatment due to study termination).

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

6. Secondary Outcome

Title	Time to Anti-HBs (Antibody to Hepatitis B Surface Antigen) Seroconversion
Time Frame	Baseline through Week 96

Outcome Measure Data

Analysis Population Description

This analysis was not done since no events of HBsAg loss were observed to to Week 36. (No participant reached Week 96 of treatment due to study termination).

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

7. Secondary Outcome

Title	Percentage of Participants With Anti-HBs Seroconversion Over Time
Time Frame	Weeks 52, 60, 72 and 96

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

8. Secondary Outcome

Title	Percentage of Participants With HBeAg Loss and Anti-Hepatitis B e Antigen (Anti-HBe) Seroconversion (if HBeAg-Positive at Study Entry) Over Time
Time Frame	Weeks 52, 60, 72 and 96

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

9. Secondary Outcome

Title	Percentage of Participants With Resistance to ARC-520 Injection by Week 52
Description	Resistance is defined as > 1.0 log IU/mL quantitative HBsAg (qHBsAg) increase from nadir, confirmed by repeat test.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

10. Secondary Outcome

Title	Percentage of Participants With Resistance to the Combination Therapy From Baseline to Week 60
Description	Resistance is defined as > 1.0 log IU/mL increase in HBV DNA from nadir, confirmed by repeat test.
Time Frame	Baseline, Week 60

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 60 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

11. Secondary Outcome

Title	Percentage of Participants With HDV With Undetectable HDV Ribonucleic Acid (RNA) After 48 Weeks of Concomitant ARC-520 Injection and PEG IFN Alpha 2a Therapy Over Time (Cohort 7 Only)
Time Frame	Weeks 52, 60, 72 and 96

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 52 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

12. Secondary Outcome

Title	Log Change From Baseline in Quantitative HBV Deoxyribonucleic Acid (DNA) Serum Levels Over Time
Time Frame	Baseline, Weeks 52, 60, 72 and 96

Outcome Measure Data

Analysis Population Description

The study was terminated prior to any participant reaching Week 60 of treatment; therefore, this outcome measure could not be analyzed.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7	Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).	Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.	Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Measure Participants	0	0	0	0	0	0	0	0

Adverse Events

Time Frame	From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up
Arm/Group Title	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6		Cohort 7		Cohort 8
Arm/Group Description	Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (2 mg/kg IV) every 4 weeks for 48 weeks (13 doses).		Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.		Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.		Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.		Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.		Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.		Treatment-naïve, HBeAg-negative or HBeAg-positive participants with HDV administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.		Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
All Cause Mortality
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6		Cohort 7		Cohort 8
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6		Cohort 7		Cohort 8
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Infections and infestations
Vestibular neuronitis	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6		Cohort 7		Cohort 8
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/10 (50%)		0/2 (0%)		4/7 (57.1%)		5/12 (41.7%)		5/11 (45.5%)		8/13 (61.5%)		9/12 (75%)		6/12 (50%)
Blood and lymphatic system disorders
Leukopenia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		4/12 (33.3%)		0/12 (0%)
Lymphopenia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		2/12 (16.7%)		0/12 (0%)
Neutropenia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		5/12 (41.7%)		0/12 (0%)
Thrombocytopenia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		2/12 (16.7%)		0/12 (0%)
Cardiac disorders
Sinus tachycardia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Ear and labyrinth disorders
Tinnitus	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Eye disorders
Eye irritation	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Constipation	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Diarrhoea	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Dry mouth	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		1/12 (8.3%)
Dyspepsia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Gastrooesophageal reflux disease	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Haemorrhoids	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Nausea	1/10 (10%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		3/13 (23.1%)		0/12 (0%)		0/12 (0%)
Vomiting	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
General disorders
Administration site bruise	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Asthenia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		1/12 (8.3%)		0/12 (0%)
Chest pain	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Chills	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		1/11 (9.1%)		2/13 (15.4%)		0/12 (0%)		0/12 (0%)
Fatigue	0/10 (0%)		0/2 (0%)		2/7 (28.6%)		0/12 (0%)		3/11 (27.3%)		3/13 (23.1%)		0/12 (0%)		1/12 (8.3%)
Feeling cold	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Feeling hot	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Hot flush	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Influenza like illness	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Injection site erythema	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Irritability	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Malaise	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Peripheral coldness	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Pyrexia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Swelling	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Hepatobiliary disorders
Hepatitis	1/10 (10%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Immune system disorders
Cytokine release syndrome	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Hypersensitivity	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Infections and infestations
Lower respiratory tract infection	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Nasopharyngitis	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Oral herpes	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		1/12 (8.3%)		0/12 (0%)
Rhinitis	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Tonsillitis	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Upper respiratory tract infection	1/10 (10%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		2/13 (15.4%)		0/12 (0%)		2/12 (16.7%)
Viral infection	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		1/12 (8.3%)		2/11 (18.2%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Viral upper respiratory tract infection	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Injury, poisoning and procedural complications
Contusion	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Infusion related reaction	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Investigations
Alanine aminotransferase increased	1/10 (10%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		1/12 (8.3%)		0/12 (0%)
Aspartate aminotransferase increased	1/10 (10%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		1/12 (8.3%)		0/12 (0%)
International normalised ratio increased	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		2/12 (16.7%)		0/12 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Diabetes mellitus	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		1/12 (8.3%)
Muscle tightness	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Myalgia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		2/13 (15.4%)		0/12 (0%)		0/12 (0%)
Pain in extremity	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		1/12 (8.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Nervous system disorders
Dizziness	2/10 (20%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		2/12 (16.7%)
Head discomfort	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Headache	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Hypoaesthesia	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Sedation	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Somnolence	1/10 (10%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		1/11 (9.1%)		2/13 (15.4%)		0/12 (0%)		0/12 (0%)
Syncope	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Tremor	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		1/12 (8.3%)		0/12 (0%)
Psychiatric disorders
Anxiety	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		1/12 (8.3%)
Euphoric mood	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		1/12 (8.3%)
Somnolence	1/10 (10%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Renal and urinary disorders
Renal colic	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Reproductive system and breast disorders
Prostatitis	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Cough	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		1/12 (8.3%)		2/11 (18.2%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Dyspnoea	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Rhinorrhoea	0/10 (0%)		0/2 (0%)		0/7 (0%)		1/12 (8.3%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Flushing	0/10 (0%)		0/2 (0%)		1/7 (14.3%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Pruritus	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Rash	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		1/11 (9.1%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Surgical and medical procedures
Hernia repair	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Skin neoplasm excision	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)
Vascular disorders
Hypotension	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		0/12 (0%)		1/12 (8.3%)
Peripheral coldness	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		0/13 (0%)		1/12 (8.3%)		0/12 (0%)
Vasoconstriction	0/10 (0%)		0/2 (0%)		0/7 (0%)		0/12 (0%)		0/11 (0%)		1/13 (7.7%)		0/12 (0%)		0/12 (0%)

Limitations/Caveats

The ARC-520 Injection development program was terminated early for regulatory and business reasons secondary to findings occurring in a non-clinical toxicology study. Program termination was not due to safety findings in humans.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.